Metabolomics Profiling Reveals Rehmanniae Radix Preparata Extract Protects against Glucocorticoid-Induced Osteoporosis Mainly via Intervening Steroid Hormone Biosynthesis

Rehmanniae Radix Preparata (RR), the dry rhizome of Rehmannia glutinosa Libosch., is a traditional herbal medicine for improving the liver and kidney function. Ample clinical and pharmacological experiments show that RR can prevent post-menopausal osteoporosis and senile osteoporosis. In the present...

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Main Authors: Tianshuang Xia, Xin Dong, Yiping Jiang, Liuyue Lin, Zhimin Dong, Yi Shen, Hailiang Xin, Qiaoyan Zhang, Luping Qin
Format: Article
Language:English
Published: MDPI AG 2019-01-01
Series:Molecules
Subjects:
Online Access:http://www.mdpi.com/1420-3049/24/2/253
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author Tianshuang Xia
Xin Dong
Yiping Jiang
Liuyue Lin
Zhimin Dong
Yi Shen
Hailiang Xin
Qiaoyan Zhang
Luping Qin
author_facet Tianshuang Xia
Xin Dong
Yiping Jiang
Liuyue Lin
Zhimin Dong
Yi Shen
Hailiang Xin
Qiaoyan Zhang
Luping Qin
author_sort Tianshuang Xia
collection DOAJ
description Rehmanniae Radix Preparata (RR), the dry rhizome of Rehmannia glutinosa Libosch., is a traditional herbal medicine for improving the liver and kidney function. Ample clinical and pharmacological experiments show that RR can prevent post-menopausal osteoporosis and senile osteoporosis. In the present study, in vivo and in vitro experiments, as well as a UHPLC-Q/TOF-MS-based metabolomics study, were used to explore the preventing effect of RR on glucocorticoid-induced osteoporosis (GIOP) and its underlying mechanisms. As a result, RR significantly enhanced bone mineral density (BMD), improved the micro-architecture of trabecular bone, and intervened in biochemical markers of bone metabolism in dexamethasone (DEX)-treated rats. For the in vitro experiment, RR increased the cell proliferation and alkaline phosphatase (ALP) activity, enhanced the extracellular matrix mineralization level, and improved the expression of runt-related transcription factor 2 (RUNX2) and osteopontin (OPN) in DEX-injured osteoblasts. For the metabolomics study, a total of 27 differential metabolites were detected in the DEX group vs. the control group, of which 10 were significantly reversed after RR treatment. These metabolites were majorly involved in steroid hormone biosynthesis, sex steroids regulation, and amino acid metabolism. By metabolic pathway and Western blotting analysis, it was further ascertained that RR protected against DEX-induced bone loss, mainly via interfering steroid hormone biosynthesis, as evidenced by the up-regulation of cytochrome P450 17A1 (CYP17A1) and aromatase (CYP19A1), and the down-regulation of 11β-hydroxysteroid dehydrogenase (HSD11B1). Collectively, these results indicated that RR had a notable preventing effect on GIOP, and the action mechanism might be related to steroid hormone biosynthesis.
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spelling doaj.art-6633ee8e3a5f4297b05170edd066f4c82022-12-22T01:46:20ZengMDPI AGMolecules1420-30492019-01-0124225310.3390/molecules24020253molecules24020253Metabolomics Profiling Reveals Rehmanniae Radix Preparata Extract Protects against Glucocorticoid-Induced Osteoporosis Mainly via Intervening Steroid Hormone BiosynthesisTianshuang Xia0Xin Dong1Yiping Jiang2Liuyue Lin3Zhimin Dong4Yi Shen5Hailiang Xin6Qiaoyan Zhang7Luping Qin8Department of Pharmacognosy, Second Military Medical University School of Pharmacy, Shanghai 200433, ChinaDepartment of Pharmacognosy, Second Military Medical University School of Pharmacy, Shanghai 200433, ChinaDepartment of Pharmacognosy, Second Military Medical University School of Pharmacy, Shanghai 200433, ChinaDepartment of Pharmacognosy, Second Military Medical University School of Pharmacy, Shanghai 200433, ChinaDepartment of Pharmacognosy, Second Military Medical University School of Pharmacy, Shanghai 200433, ChinaDepartment of Pharmacognosy, Second Military Medical University School of Pharmacy, Shanghai 200433, ChinaDepartment of Pharmacognosy, Second Military Medical University School of Pharmacy, Shanghai 200433, ChinaDepartment of Pharmacognosy, Second Military Medical University School of Pharmacy, Shanghai 200433, ChinaDepartment of Pharmacognosy, Second Military Medical University School of Pharmacy, Shanghai 200433, ChinaRehmanniae Radix Preparata (RR), the dry rhizome of Rehmannia glutinosa Libosch., is a traditional herbal medicine for improving the liver and kidney function. Ample clinical and pharmacological experiments show that RR can prevent post-menopausal osteoporosis and senile osteoporosis. In the present study, in vivo and in vitro experiments, as well as a UHPLC-Q/TOF-MS-based metabolomics study, were used to explore the preventing effect of RR on glucocorticoid-induced osteoporosis (GIOP) and its underlying mechanisms. As a result, RR significantly enhanced bone mineral density (BMD), improved the micro-architecture of trabecular bone, and intervened in biochemical markers of bone metabolism in dexamethasone (DEX)-treated rats. For the in vitro experiment, RR increased the cell proliferation and alkaline phosphatase (ALP) activity, enhanced the extracellular matrix mineralization level, and improved the expression of runt-related transcription factor 2 (RUNX2) and osteopontin (OPN) in DEX-injured osteoblasts. For the metabolomics study, a total of 27 differential metabolites were detected in the DEX group vs. the control group, of which 10 were significantly reversed after RR treatment. These metabolites were majorly involved in steroid hormone biosynthesis, sex steroids regulation, and amino acid metabolism. By metabolic pathway and Western blotting analysis, it was further ascertained that RR protected against DEX-induced bone loss, mainly via interfering steroid hormone biosynthesis, as evidenced by the up-regulation of cytochrome P450 17A1 (CYP17A1) and aromatase (CYP19A1), and the down-regulation of 11β-hydroxysteroid dehydrogenase (HSD11B1). Collectively, these results indicated that RR had a notable preventing effect on GIOP, and the action mechanism might be related to steroid hormone biosynthesis.http://www.mdpi.com/1420-3049/24/2/253Rehmanniae Radix Preparataglucocorticoid-induced osteoporosismetabolomicsosteoblaststeroid hormone biosynthesis
spellingShingle Tianshuang Xia
Xin Dong
Yiping Jiang
Liuyue Lin
Zhimin Dong
Yi Shen
Hailiang Xin
Qiaoyan Zhang
Luping Qin
Metabolomics Profiling Reveals Rehmanniae Radix Preparata Extract Protects against Glucocorticoid-Induced Osteoporosis Mainly via Intervening Steroid Hormone Biosynthesis
Molecules
Rehmanniae Radix Preparata
glucocorticoid-induced osteoporosis
metabolomics
osteoblast
steroid hormone biosynthesis
title Metabolomics Profiling Reveals Rehmanniae Radix Preparata Extract Protects against Glucocorticoid-Induced Osteoporosis Mainly via Intervening Steroid Hormone Biosynthesis
title_full Metabolomics Profiling Reveals Rehmanniae Radix Preparata Extract Protects against Glucocorticoid-Induced Osteoporosis Mainly via Intervening Steroid Hormone Biosynthesis
title_fullStr Metabolomics Profiling Reveals Rehmanniae Radix Preparata Extract Protects against Glucocorticoid-Induced Osteoporosis Mainly via Intervening Steroid Hormone Biosynthesis
title_full_unstemmed Metabolomics Profiling Reveals Rehmanniae Radix Preparata Extract Protects against Glucocorticoid-Induced Osteoporosis Mainly via Intervening Steroid Hormone Biosynthesis
title_short Metabolomics Profiling Reveals Rehmanniae Radix Preparata Extract Protects against Glucocorticoid-Induced Osteoporosis Mainly via Intervening Steroid Hormone Biosynthesis
title_sort metabolomics profiling reveals rehmanniae radix preparata extract protects against glucocorticoid induced osteoporosis mainly via intervening steroid hormone biosynthesis
topic Rehmanniae Radix Preparata
glucocorticoid-induced osteoporosis
metabolomics
osteoblast
steroid hormone biosynthesis
url http://www.mdpi.com/1420-3049/24/2/253
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